Ex vivo effects of high-density lipoprotein exposure on the lipopolysaccharide-induced inflammatory response in patients with severe cirrhosis

✍ Scribed by Arnaud Galbois; Dominique Thabut; Khalid A. Tazi; Marika Rudler; Morvarid Shir Mohammadi; Dominique Bonnefont-Rousselot; Hind Bennani; Annie Bezeaud; Zera Tellier; Cécile Guichard; Nicolas Coant; Eric Ogier-Denis; Richard Moreau; Didier Lebrec

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 538 KB
• Volume: 49
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.22582

✦ Synopsis

High

-density lipoproteins (HDL) are known to neutralize lipopolysaccharide (LPS). Because patients with cirrhosis have lower HDL levels, this may contribute to LPS-induced ex vivo monocyte overproduction of proinflammatory cytokines. However, the effects of HDL on cytokine production by monocytes from patients with cirrhosis have never been studied. The aim of this study was to determine the effects of HDL on LPS-induced proinflammatory cytokine production in whole blood and isolated monocytes from patients with severe cirrhosis and controls. Plasma levels of HDL and cytokines were determined. The effects of reconstituted HDL (rHDL) on LPS-induced cytokine production in whole blood were assessed by cytokine array and on tumor necrosis factor alpha (TNF-␣) and interleukin-10 (IL-10) production in isolated monocytes. Plasma HDL levels were significantly lower in patients with cirrhosis than in controls. Plasma levels of TNF-␣ and IL-6 were significantly higher in patients with cirrhosis than in controls. Incubation of rHDL with whole blood prevented LPS-induced TNF-␣ and IL-6 overproduction in patients with cirrhosis. LPS-induced TNF-␣ production and CD14 expression were significantly more marked in cirrhotic monocytes than in control monocytes, and both decreased significantly after rHDL incubation. LPS-induced down-regulation of scavenger receptor, class B, type I (SR-BI) expression was abolished in cirrhotic monocytes. Conclusions: This study shows that rHDL abolishes the LPS-induced overproduction of proinflammatory cytokines in whole blood from patients with severe cirrhosis. These results were confirmed in isolated monocytes from these patients. This suggests that administration of rHDL might be a useful strategy for the treatment of cirrhosis to limit LPS-induced cytokine overproduction. (HEPATOLOGY 2009;49:175-184.)

I n patients with cirrhosis, gram-negative bacterial infections induce an overproduction of the proinflammatory cytokine tumor necrosis factor alpha (TNF-␣), which is involved in both systemic vasodilatation 1,2 and progression of liver injury. 3 Moreover mortality from septic shock reaches 80% in patients with cirrhosis 4 compared with 30% in patients without. 5 In case of infection, increased TNF-␣ production is much higher in patients with than in those without cirrhosis. 6 It has also been demonstrated that administration of or exposure to lipopolysaccharide (LPS) induces marked TNF-␣ production in vivo in cirrhotic rats 7,8 and ex vivo in monocytes from patients with cirrhosis. 9 Recently, it was shown that monocytes from patients with severe cirrhosis were spontaneously activated to produce proinflammatory cytokines and exhibited a hyperresponsiveness to LPS. [10][11][12] High-density lipoprotein (HDL) particles are multifunctional lipoprotein complexes that transport lipids and have several anti-inflammatory properties. 13 These include lipid transport and antioxidant activities that re-